– AA-T3A-C12 is an anisamide ligand-tethered lipidoid (AA-lipidoid) with high potency and selectivity to deliver RNA payloads to activated fibroblasts. HSP47 siRNA (siHSP47)-loaded AA-T3A-C12 LNP achieves ~65% knockdown and dramatically reduces liver fibrosis, which significantly outperforms the benchmark DLin-MC3-DMA (MC3) LNP.